Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein

Glenn C. Telling; Michael Scott; Karen K. Hsiao; Dallas Foster; Shu Lian Yang; Marilyn Torchia; Katie C.L. Sidle; John Collinge; Stephen J. Dearmond; Stanley B. Prusiner

doi:10.1073/pnas.91.21.9936

Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein

Glenn C. Telling, Michael Scott, Karen K. Hsiao, Dallas Foster, Shu Lian Yang, Marilyn Torchia, Katie C.L. Sidle, John Collinge, Stephen J. Dearmond, Stanley B. Prusiner

Neurology

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280 Scopus citations

Abstract

Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease ≃200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrP(Sc) (where PrP(Sc) is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrP(Sc). The patterns of MHu2MPrP(Sc) and MoPrP(Sc) accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease >500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.

Original language	English (US)
Pages (from-to)	9936-9940
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	91
Issue number	21
DOIs	https://doi.org/10.1073/pnas.91.21.9936
State	Published - Oct 11 1994

Keywords

bovine spongiform encephalopathy
human growth hormone
prion propagation
scrapie
species barrier

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.91.21.9936

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Telling, G. C., Scott, M., Hsiao, K. K., Foster, D., Yang, S. L., Torchia, M., Sidle, K. C. L., Collinge, J., Dearmond, S. J., & Prusiner, S. B. (1994). Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proceedings of the National Academy of Sciences of the United States of America, 91(21), 9936-9940. https://doi.org/10.1073/pnas.91.21.9936

Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. / Telling, Glenn C.; Scott, Michael; Hsiao, Karen K. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 21, 11.10.1994, p. 9936-9940.

Research output: Contribution to journal › Article › peer-review

Telling, GC, Scott, M, Hsiao, KK, Foster, D, Yang, SL, Torchia, M, Sidle, KCL, Collinge, J, Dearmond, SJ & Prusiner, SB 1994, 'Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 21, pp. 9936-9940. https://doi.org/10.1073/pnas.91.21.9936

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abstract = "Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease ≃200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrP(Sc) (where PrP(Sc) is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrP(Sc). The patterns of MHu2MPrP(Sc) and MoPrP(Sc) accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease >500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.",

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AU - Telling, Glenn C.

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AU - Foster, Dallas

AU - Yang, Shu Lian

AU - Torchia, Marilyn

AU - Sidle, Katie C.L.

AU - Collinge, John

AU - Dearmond, Stephen J.

AU - Prusiner, Stanley B.

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Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein

Abstract

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UN SDGs

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